Prevalence Rates of Pneumococcal Vaccination in IBD and 30-Day Clinical Outcomes in Patients With IBD and Pneumococcal Disease Stratified by Receipt of Pneumococcal Vaccination: A Multi-Network Study


 This study sought to assess outcomes associated with pneumococcal vaccination in adult inflammatory bowel disease patients. Results found unvaccinated patients had higher adverse outcomes, including greater risk of hospitalization, ICU admission, ventilation, and mortality. These findings underscore the importance of pneumococcal vaccination.


Introduction
Streptococcus pneumoniae is a pathogen responsible for a number of illnesses including pneumonia, sepsis, and meningitis.Approximately 150 000 hospitalizations yearly in the United States occur from pneumococcal pneumonia, with a 5%-7% case fatality rate. 1 Patients with inflammatory bowel disease (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), are at increased risk for developing pneumococcal disease due to their altered immune systems and treatment with immunosuppressive agents. 2,3This elevated risk has led to the recommendation that patients with IBD be vaccinated against streptococcal disease, particularly if on immunosuppression. 4 Despite this recommendation, prior work has shown highly variable rates of vaccination among IBD patients ranging from 10% to 60%. 5 Given the highly variable rates of pneumococcal vaccination in IBD reported in literature, we sought to characterize the rates of pneumococcal vaccination utilization in IBD patients utilizing a large population-based database.Additionally, we assessed clinical outcomes of rates of hospitalization, ICU admission, mechanical ventilation, and all-cause mortality within 30 days of pneumococcal infection among IBD patients with pneumococcal disease, stratified by vaccination.

Methods
A retrospective cohort study was performed using TriNetX (Cambridge, MA), a multi-institutional database containing data from over 70 million patients across 58 US healthcare organizations between 2002 and 2022.Patients with IBD were defined as individuals carrying a diagnosis of UC or CD per ICD-10-CM coding and a prescription for at least 1 IBD-specific medication identified utilizing LOINC codes: Nonadvanced therapies: Mesalamine, sulfasalazine, balsalazide, budesonide; advanced therapies: azathioprine, methotrexate, 6-mercatopurine, infliximab, certolizumab, golimumab, adalimumab, vedolizumab, ustekinumab, tofacitinib, upadacitinib, and risankizumab.Pneumococcal vaccination was defined as recorded pneumococcal polysaccharide vaccine (PPSV23), pneumococcal conjugate vaccine (PCV13), or encounter for pneumococcal vaccine Ford et al administration.We evaluated overall rates of vaccination among IBD and stratified them by 10-year age intervals, race, sex, and risk factors for severe pneumonia.
For outcomes, index event was pneumococcal infection occurrence defined by ICD coding for pneumonia (ICD-10-CM J13), sepsis (A41), or meningitis (G03) due to Streptococcus pneumoniae.Patients with IBD were then stratified by receipt of pneumococcal vaccine (case group: IBD patients with pneumococcal vaccination) or not (control group: IBD patients without pneumococcal vaccination).We then assessed outcomes among IBD patients with pneumococcal disease.Coprimary outcomes included rates of hospitalization, ICU admission, mechanical ventilation, and all-cause mortality within 30 days of pneumococcal infection.
Patients were then 1:1 propensity score matched by demographics including age, race, and sex, and risk factors for developing severe pneumonia including obesity, chronic obstructive pulmonary disease (COPD), asthma, and smoking.Odds ratios (ORs) were calculated for each outcome compared between the vaccinated and unvaccinated patients.For continuous data, analyses were conducted using independent t-tests, while chi-square tests were performed for categorical data.All tests were 2-tailed with an alpha level of .05.
Of the 32 186 vaccinated patients, of those prescribed IBD medications, 12 199 (37.9%) had received nonadvanced therapies, while 19 987 (62.1%) had received advanced therapies.When stratified by age, younger patients were vaccinated more frequently if they had a history of advanced therapy prescription compared to patients not on advanced therapy (ie, among vaccinated patients 18-30 years old, 4337 [89.7%] had advanced therapy compared to 497 [10.3%] with nonadvanced; Table 4).This trend of higher proportion of younger patients with IBD being vaccinated if they were

Discussion
This is one of the largest studies to date evaluating the rates of pneumococcal vaccination uptake in IBD and its efficacy.
Our finding of a 15% vaccination rate is on the lower end of rates of 10%-60% 5 as reported in prior studies on pneumococcal vaccination among IBD patients; Case et al. found a vaccination rate of 20% among IBD patients, while Love et al. found a rate of 42%. 6,7This difference may stem from the former studies' use of Veterans' Affairs (VA) data, while ours incorporates data from across a wider array of healthcare systems with potentially varying vaccination practices.However, our observation that vaccination was higher among older patients is in line with this previous work. 7][10][11][12][13] Most importantly, given the significantly large sample size of 221 957 patients in this study, our findings have greater validity compared to prior studies.As for outcomes of pneumococcal disease among IBD patients, we found that pneumococcal vaccination was significantly protective against hospitalization, ICU admission, mechanical ventilation, and mortality within 30 days of pneumococcal disease diagnosis.This finding is similar to Love et al.'s recent work demonstrating that vaccination was protective against severe pneumococcal disease among VA patients. 6his is the largest study to date assessing rates of pneumococcal vaccination and outcomes of pneumococcal disease among IBD patients to our knowledge.Aside from a large Ford et al sample size, additional strengths of our study include propensity matching to control for potential confounding variables.Limitations of our study include the use of billing codes, retrospective cohort analysis, and the inability to detect vaccination status if patients received vaccination outside of HCOs covered by TrinetX which may have led us to underestimate vaccination rates.The former-most limitation is mitigated by including IBD-specific medication prescription as a factor in defining IBD, thereby increasing the sensitivity.However, this strategy limits the ability to determine the effect of IBDspecific medications on the development of severe pneumococcal disease.Further, previous work has demonstrated that administrative data such as billing codes can be highly accurate in identifying patients with pneumococcal disease, particularly when combined with prescription codes. 14n conclusion, in the largest retrospective cohort study to date on pneumococcal vaccination rates in IBD, we found an overall vaccination rate of 15% and significantly lower rates of vaccination against pneumococcal disease among younger patients, though younger patients who were vaccinated tended to have a history of advanced IBD therapy.It additionally showed an increased risk of hospitalization, ICU admission, mechanical ventilation, and mortality among IBD patients not vaccinated against pneumococcal disease.These findings call for the implementation of system-based programs to improve rates of pneumococcal vaccination in IBD to prevent adverse outcomes.

Figure 1 .
Figure 1.Pneumococcal vaccination rates in patients with inflammatory bowel disease stratified by age.

Table 1 .
Pneumococcal vaccination rates in patient with IBD stratified by risk factors for severe pneumonia p value.

Table 2 .
Demographic distribution (race, gender) and prevalence of risk factors for severe pneumococcal infection in index cohort of IBD patients with pneumococcal infection stratified by vaccination status, prior to propensity score matching p value.

Table 3 .
30-Day outcomes after pneumococcal infection in IBD patients stratified by vaccination status, after propensity score matching for demographics and risk factors for severe pneumococcal infection p value.

Table 4 .
Medications prescribed among patients having received pneumococcal vaccination p value.